Scriver C R, Nowacki P M
Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
J Inherit Metab Dis. 1999 Jun;22(4):519-30. doi: 10.1023/a:1005560408119.
Mutations are the source of genetic variation and diversity; by their effect, some are neutral, others are pathogenic. In contemporary genetics, mutations appear at the interface between genomics (structural and functional) and genetics (heredity), where they serve gene discovery and mapping (genomics) and generate challenges to modify their phenotypic effects (medical genetics). Assuming the human genome harbours 80,000 transcribed genes each possessing at least 100 different (germline) alleles in a typical population, how then to record and recover data on at least 8 million human alleles? Bioinformatics is the essential resource to create the corresponding accessible digital libraries (genomic and locus-specific mutation databases) for this purpose, a goal to which The HUGO Mutation Database Initiative (Science 279: 10-11, 1998) aspires. Guidelines now exist for naming alleles (Hum Mutat 11: 1-3, 1998). The principles behind the practice are illustrated by PAHdb (http:/(/)www.mcgill.ca/ pahdb), a prototype locus-specific mutation database (NAR 26: 220-225, 1998), and by prototype genomic mutation databases (HGMD (NAR 26: 285-287, 1998), http:/(/)www.uwcm.ac.uk/uwcm/mg/hgmd0.h tml; the EBI mutation database, http:/(/)www2.ebi.ac.uk/mutations/; and OMIM, http:/(/)www.ncbi.nlm. nih.gov/Omim.html).
突变是遗传变异和多样性的来源；就其作用而言，有些是中性的，有些是致病的。在当代遗传学中，突变出现在基因组学（结构和功能）与遗传学（遗传）的交叉点上，在那里它们有助于基因发现和定位（基因组学），并对改变其表型效应（医学遗传学）提出挑战。假设人类基因组包含80000个转录基因，在一个典型人群中每个基因至少有100个不同的（种系）等位基因，那么如何记录和恢复至少800万个人类等位基因的数据呢？生物信息学是为此创建相应的可访问数字文库（基因组和基因座特异性突变数据库）的重要资源，这是人类基因组组织突变数据库计划（《科学》279：10 - 11，1998年）所追求的目标。现在已经有了命名等位基因的指导原则（《人类突变》11：1 - 3，1998年）。PAHdb（http:/(/)www.mcgill.ca/ pahdb），一个基因座特异性突变数据库原型（《核酸研究》26：220 - 225，1998年），以及基因组突变数据库原型（HGMD（《核酸研究》26：285 - 287，1998年），http:/(/)www.uwcm.ac.uk/uwcm/mg/hgmd0.h tml；欧洲生物信息学研究所突变数据库，http:/(/)www2.ebi.ac.uk/mutations/；以及在线孟德尔人类遗传数据库，http:/(/)www.ncbi.nlm.nih.gov/Omim.html）说明了这种做法背后的原则。
